The efficacy and safety of doxazosin (n = 83) and atenolol (n = 81) have been compared during a 3-year period. Doxazosin (mean dose at 3 years, 5.2 mg/day) and atenolol (mean dose, 66.4 mg/day) produced a sustained and overall similar reduction in blood pressure, with no evidence of tolerance. Doxazosin decreased mean blood pressure from 158/104 mm Hg to 146/90 mm Hg; with atenolol the decrease was from 160/103 mm Hg to 144/88 mm Hg. Whereas the reduction in blood pressure with atenolol was paralleled by a significant (p less than 0.05) decrease in heart rate (from a mean of 74 to 60 beats/min), doxazosin produced no clinically meaningful changes in heart rate. In contrast to atenolol, doxazosin reduced triglyceride levels by -5.9% (atenolol +22.5%), increased high-density lipoprotein cholesterol levels by +3.7% (atenolol, -11.2%), and increased the high-density lipoprotein/total cholesterol ratio by +5.9% (atenolol, -10.3%); all of these values were significantly (p less than 0.001) different from those of atenolol-treated patients. Doxazosin also reduced the calculated low-density lipoprotein cholesterol levels by -3.3% (atenolol, unchanged). The adverse effect of atenolol on lipid levels apparently negated any beneficial effect of blood pressure reduction, because the calculated coronary heart disease (CHD) risk actually increased significantly. In contrast, the reduction in calculated CHD risk in the doxazosin group was statistically significant at all points during the study. The safety profile of the drugs was similar. With the added potential of the reduction in the calculated risk of CHD among hypertensive patients,doxazosin represents an appropriate first-line drug for the treatment of essential hypertension.